Day 13: Evolutionary Developmental Biology

Some snakes have vestigial hind limbs! Fossil snakes have been found with hind limbs. What is the general consensus regarding the loss of its forelimbs and hindlimbs?

*Separate* loss of forelimbs and hindlimbs

Developmental genes have many pleiotropic effects, therefore...

*natural selection* on one function may be *limited/influenced* by another function (trade-off).

evolutionary implications of developmental biology: Rapid evolutionary leaps in phenotype: - can result from _______ - Example _______ - What does this imply?

- can result from a *relatively minor change* in a *developmental process*, specifically, a *change in the expression* of one or a few genes - Ex: loss of hind limbs in snakes due to alteration of ZRS, which is essential for expression of Shh (required for proper limb development) *evolution is not always gradual*

What are 3 evolutionary implications of developmental biology?

1) *Rapid evolutionary leaps* in phenotype/morphology 2) Many *developmental genes* are *pleiotropic* - Ex: Shh 3) *Conserved developmental processes* may lead to *parallel evolution*

Many developmental genes are pleiotropic... what does this imply?? (2 things)

1) Evolution involves *re-use* and *re-purposing* of *ancestral gene networks* 2) Natural selection on one function may be limited/influenced by another function (*trade-off*) - Ex: Stickleback Ectodysplasin allele (LL) responsible for loss of armor in freshwater species is also responsible for faster growth rate

Ancestrally, vertebrates have 4 ____________ on different chromosomes, likely generated via...

1) Hox gene clusters 2) x2 whole genome duplication

__________ and _________, as well as many other kinds of ________ are critical in the development of the basic body plan

1) Hox genes 2) other homeobox genes 3) highly conserved *regulatory gene networks*

Hard to determine if ________ in mice and _______ in flies are derived from same ancestral gene

1) Hox genes (e.g. Hox4) 2) Dfd

Zone of Polarizing Activity Regulatory Sequence (ZRS) - what is it? - what is its function? - where is it located?

1) highly conserved region of DNA 2) regulates the sonic hedgehog (Shh) gene - controls tissue specific expression 3) located in an intron of the limb development membrane protein 1 gene.

A _________ or ___________, can lead to entirely different organs developing in new parts of the body.

1) mutation in a Hox gene 2) expression of a Hox gene at a new time or in a new place

evolutionary implications of developmental biology: Conserved developmental processes may lead to parallel evolution, which is __________. This is in contrast to __________.

1) similar outcomes following similar selection pressures. 2) convergent evolution - similar outcomes occur due to similar selective pressures but the developmental mechanism is different.

Conservation of ancestral developmental mechanisms enables __________ resulting in ________, challenging the idea that _________

1) similar solutions to the same ecological problems 2) parallel evolution 3) variation has no direction and direction only comes from selection.

evolutionary implications of developmental biology: Many developmental genes are pleiotropic, which means...

1) they have different functions: 2) They turn on *repeatedly* at *different times and places* during development - Ex: SHH (development of the brain and spinal cord, eyes, limbs, and many other parts of the body).

Hox genes =

A family of homeobox genes that regulate genes involved body plan development - specifically control anterior to posterior axis. - first homeobox genes to be discovered

Imagine you discover a new gene and the amino acid sequence it encodes includes a homeodomain, what can you infer from this? A) It can regulate transcription B) It will be involved in the development of the head to tail body plan C) It will be expressed in a spatial pattern that mirrors its arrangement on the chromosome D) It is a hox gene

A) It can regulate transcription B & C are properties of Hox genes

Homeobox =

Ancient, conserved (found in flies, humans, grass and fungi) DNA binding region found in all homeobox genes 1) only 180-base-pairs in length 2) codes for the homeobox domain (protein that functions as a transcription factor). 3) It binds DNA (or RNA), allowing a protein with a homeodomain to regulate transcription of other genes

What are hox genes and why are they important, pick the best explanation A) Hox genes regulate the transcription of all other genes in the genome B) Hox genes regulate the transcription of other genes determining the head to tail body plan of many organisms. C) Homeobox genes regulate hox genes and determine the head to tail body plan of many organisms D) Hox genes determine how body structures like eyes or spinal cords are built.

B) Hox genes regulate the transcription of other genes determining the head to tail body plan of many organisms.

evolutionary implications of developmental biology: Conserved developmental processes may lead to parallel evolution... what does this imply?

Bias in *production of phenotypic variation* due to *developmental factors* - remember we mentioned developmental constraints may prevent adaptations from being optimal. - Contra to idea that all directional evolution is due to selection.

If we share ~99% of our DNA with chimps how can we be so different?

Changes in *regulatory genes* (and thus gene regulation) during development.

in very simple terms, what is developmental biology? how is it commonly studied?

Developmental Bio = "process by which organisms grow and develop" - commonly studied by investigating "the genetic regulation of cell growth, differentiation and morphogenesis"

True/False: Hox genes are unique to vertebrates

False

_______________ regulate the transcription of other genes

Homeobox domains

Shh and ZRS in humans: congenital abnormalities?

Mutations in the same regulatory regions (ZRS) have been linked to a range of congenital human abnormalities, including limb malformations such as preaxial polydactyly.

Sonic Hedgehog

Protein encoded by the Sonic Hedgehog gene: plays a role in: 1) cell *growth 2) cell *specialization* 3) the normal shaping (*patterning*) of the body. important for development of many body parts including: 1) the brain and spinal cord (CNS) 2) eyes 3) limbs

How did the snake lose its forelimbs?

Vertebrates: - forelimb develops immediately anterior to a domain of HoxC-6 expression. Snakes: - HoxC-6 and HoxC-8 are expressed along the body to develop thoracic vertebrae *HoxC-6 doesn't stop being expressed therefore no signal for forelimb development*

Limb loss in snakes: transgenic mice experiments

ZRS controls the expression of Sonic hedgehog (SHH) in developing limb buds - Small 17 bp snake-specific deletion causes limb loss

spatial colinearity is not necessary...

for correct gene expression along the body axis in many organisms

Hox genes are expressed...

in a spatial pattern that mirrors their arrangement on the chromosome! *spatial colinearity*

Relatively minor changes in a developmental process or, more specifically, in the expression of one or a few genes can result in...

major *phenotypic* changes, challenging the idea that evolution is entirely gradual.

Changes in gene regulation during development can result in...

major changes in the *body plan*

Changes in gene regulation by homeobox genes and other regulatory sequences during development can result in...

major changes in the body plan e.g. limb loss.

evolutionary implications of developmental biology: Conserved developmental processes may lead to parallel evolution... give an example

mangrove habit in plants evolved in distantly related plants in saltwater - Salt tolerant leaves via high expression of Abscisic acid (ABA)

issues with SHH are associated with human diseases such as...

microphthalmia

Mutations in __________ have the potential to cause major changes in body plan

regulatory genes *rapid evolutionary leaps in phenotype can occur*

what does "highly conserved" refer to?

same sequence found in many different distantly related organisms

How the snake lost its hindlimbs

the *timing of expression* of the sonic hedgehog (Shh) gene is critical to normal hind limb development - Shh is regulated by Zone of Polarizing Activity Regulatory Sequence (ZRS) - *Changes to ZRS can cause limb loss in snakes* - If you turn the genes back on you should be able to get the development of legs in snakes

Evolutionary Developmental Biology explores...

the mechanisms of development and how these mechanisms: 1) have been *influenced by evolutionary forces* 2) *influence phenotypic evolution*